When religious freedom clashes with access to care.

n engl j med 371;7 nejm.org august 14, 2014 596 penetrant genetic mutations that predictably result in disease, clinical sequencing will enable individual screening, monitoring, prevention, and treatment of medically actionable conditions. On the other hand, there will be a large proportion of potentially deleterious variants associated with medium-sized odds ratios for disease and variable phenotypic predictive power. In keeping with evidence-based clinical decision making, such biomarkers should be used in conjunction with clinical observation, laboratory tests, and empirical treatment to refine estimates of the probability of disease and treatment prognoses. For example, knowledge about CYP2C9 mutations in cytochrome P-450 should lead to the development of decision-support tools that influence the administration of warfarin and other drugs that use the same metabolic pathways. Ultimately, clinical use of sequencing data should reduce the cost of care. If genetic information can be stored, analyzed, and disseminated in a private, costeffective, and timely manner, precise and affordable molecular and genetic diagnoses should result in more specific treatment guidelines and avoidance of costly diagnostic and therapeutic procedures. Furthermore, supplementing clinical intuition with molecular diagnoses in syndromes with overlapping symptoms may reduce variance in diagnosis and treatment outcomes between academic medical centers and community hospitals and clinics. Although additional molecular and informatics research is needed, we are confident that NGS will eventually revolutionize clinical care just as it is revolutionizing the scientific endeavor.